Peptides are important in biological processes. For example, peptides can serve as hormones, enzyme inhibitors, substrates, neurotransmitters, neuromediators, as well as many other functions. Peptides can bind to receptors or enzymes and thus influence intercellular communication and control vital cell functions such as metabolism, immune defense and reproduction (Babine et al., Chem. Rev. 1997, 97, 1359). Hence, there is an interest for using peptides in medicinal chemistry as therapeutic agents and in pharmaceutical applications.
The utility of unmodified peptides as therapeutics and pharmaceuticals have been limited by several factors. These limitations include poor metabolic stability such as susceptibility to peptidase degradation, poor cell penetrability, and lack of binding specificity due to conformational flexibility. Attempts to improve these limiting properties have been described and include generation of cyclic peptides and peptidomimetics by a variety of methods, including disulfide bond formation, amide bond formation, and carbon-carbon bond formation (Jackson et al. (1991), J. Am. Chem. Soc. 113:9391-9392; Phelan et al. (1997), J. Am. Chem. Soc. 119:455-460; Taylor (2002), Biopolymers 66: 49-75; Brunel et al. (2005), Chem. Commun. (20):2552-2554; Hiroshige et al. (1995), J. Am. Chem. Soc. 117: 11590-11591; Blackwell et al. (1998), Angew. Chem. Int. Ed. 37:3281-3284; Schafineister et al. (2000), J. Am. Chem. Soc. 122:5891-5892). These approaches are still limited by factors including poor metabolic stability (disulfide and amide bonds), poor cell penetrability (disulfide and amide bonds), and the use of potentially toxic metals (for carbon-carbon bond formation). In particular, the presence of toxic metal impurities may pose a significant challenge to the clinical use of polypeptide drugs which are manufactured via chemical reactions that require such metals, for example in the form of catalysts. Therefore, there is a need for methods of purifying peptidomimetic compounds and for the pure compositions generated by such methods.